PROJECT SUMMARY/ABSTRACT Liver cancer, the second leading cause of cancer-related death globally, is frequently diagnosed in the advanced stages of the disease, where curative treatments are either unavailable or provide only modest survival improvement. As recent studies have uncovered the natural and beneficial role of bacteria throughout the human body, as well as their proclivity to grow inside solid tumors, bacteria emerge as a natural delivery vehicle for novel therapeutics against the disease. Here we will use synthetic biology to engineer bacteria that produce high local concentrations of therapeutics targeting pathways commonly dysregulated in hepatocellular carcinoma (HCC), and that are only capable of growing within a tumor?s unique microenvironment, thereby minimizing systemic effects. Using in vitro and in vivo humanized mouse models, we aim to develop an effective, safe, and novel treatment option for HCC.